Michitaka Honda

Ramelteon for the treatment of insomnia in adults: a systematic review and meta-analysis.

Ramelteon is the first selective melatonin receptor agonist and currently is approved in the United States and Japan for the treatment of insomnia. Our meta-analysis assessed the efficacy and safety of ramelteon for the treatment of insomnia in adults. We included both published and unpublished data from randomized placebo-controlled trials evaluating the efficacy of ramelteon in adults with insomnia in the analysis. Our primary outcomes were sleep quality, subjective sleep latency (sSL), and subjective total sleep time (sTST). Secondary outcomes included latency to persistent sleep (LPS), total sleep time (TST), sleep efficiency (SE), proportion of rapid eye movement (REM) sleep, wakefulness after sleep onset (WASO), subjective WASO, number of nighttime awakenings (NAW), subjective NAW, and adverse events. Thirteen trials involving 5812 patients with insomnia or insomnia symptoms with a mean study duration of 38 days were pooled. Ramelteon was associated with reduced sSL (weighted mean difference [WMD], -4.30 min [95% confidence interval {CI}, -7.01 to -1.58]) and improved sleep quality (standardized mean differences, -0.074 [95% CI, -0.13 to -0.02]) but was not associated with increased sTST. Ramelteon also was associated with improvement in LPS, SE, and TST. The only significant adverse event was somnolence. Short-term use of ramelteon was associated with improvement in some sleep parameters in patients with insomnia, but its clinical impact is small. Long-term trials are needed before solid conclusions can be established.

Hand-sewn versus mechanical esophagogastric anastomosis after esophagectomy: a systematic review and meta-analysis.

OBJECTIVE To evaluate the risks and benefits of using a circular stapler (CS) compared with the hand-sewn (HS) method for the esophagogastric anastomosis after esophageal resection. BACKGROUND DATA Previous randomized controlled trials (RCTs) indicated that the use of a CS might prevent anastomotic leakage, whereas it was more likely to lead to anastomotic strictures. The relative efficacy of this intervention in comparison with the HS method has not been conclusively determined. METHODS A systematic review and meta-analysis of all RCTs that compared HS versus mechanical anastomosis using a CS was conducted regarding the leakage, strictures, operative time, and mortality. The study protocol was established a priori according to the recommendations of the Cochrane Collaboration. RESULTS Twelve RCTs were included with a total of 1407 patients. The use of a CS, compared with the HS method, (1) led to no significant difference in the incidence of anastomotic leakage [risk ratio (RR): 1.02, 95% confidence interval (CI): 0.66-1.59] or postoperative mortality (RR: 1.64, 95% CI: 0.95-2.83), (2) increased the incidence of anastomotic strictures (RR: 1.67, 95% CI: 1.16-2.42), and (3) reduced the length of the operation time (mean: -15.3 minutes, range: -28.1 to -2.39). For these results, a subgroup analysis and a meta-regression analysis yielded no significant differences for the anastomotic site, diameter of the CS, layer, or configuration. CONCLUSION The use of a CS contributed to reducing the length of the operation, but was associated with an increased risk of anastomotic strictures. Both the CS and the HS method are viable alternatives in the reconstruction after esophagectomy.

Long-term Outcomes of Laparoscopic Versus Open Surgery for Clinical Stage I Gastric Cancer: The LOC-1 Study.

Background: Clinical trials comparing laparoscopic gastrectomy (LG) versus traditional open gastrectomy (OG) have been planned, their surgical outcomes reported but their oncologic outcomes are still pending. Consequently, we have conducted this large-scale historical cohort study to provide relevant information rapidly to guide our current practice. Methods: Through a consensus meeting involving surgeons, biostatisticians, and epidemiologists, 30 variables of preoperative information possibly influencing surgeons’ choice between LG versus OG and potentially associating with outcomes were identified to enable rigorous estimation of propensity scores. A total of 4235 consecutive patients who underwent gastrectomy for gastric adenocarcinoma were identified and their relevant data were gathered from the participating hospitals. After propensity score matching, 1848 patients (924 each for LG and OG) were selected for comparison of long-term outcomes. Results: In the propensity-matched population, the 5-year overall survival was 96.3% [95% confidence interval (CI) 95.0–97.6] in the OG as compared with 97.1% (95% CI, 95.9–98.3) in LG. The number of all-cause death was 33/924 in the OG and 24/924 in the LG through the entire period, and the hazard ratio (LG/OG) for overall death was 0.75 (95% CI, 0.44–1.27; P = 0.290). The 3-year recurrence-free survival was 97.4% (95% CI, 96.4–98.5) in the OG and 97.7% (95% CI, 96.5–98.8) in the LG. The number of recurrence was 22/924 in the OG and 21/924 in the LG through the entire period, and the hazard ratio was 1.01 (95% CI, 0.55–1.84; P = 0.981). Conclusions: This observational study adjusted for all-known confounding factors seems to provide strong enough evidence to suggest that LG is oncologically comparable to OG for gastric cancer.

Clinicopathological analysis of ten patients with metaplastic squamous cell carcinoma of the breast

PurposePrimary squamous cell carcinoma (SCC) and metaplastic squamous cell carcinoma (MSCC) are rare types of breast cancer with specific histological features. They are characterized by rapid progression, a tendency toward cyst formation, and negativity for hormone receptors. Many studies have concluded that SCC of the breast carries a poor prognosis, based on the fact that conventional chemotherapy for ductal carcinoma of the breast is ineffective against SCC. This is a retrospective study of patients in a single center with SCC or MSCC.MethodsWe searched the records of the Tokyo Metropolitan Komagome Hospital for patients diagnosed with breast SCC or MSCC between 1979 and 2006. Squamous cell carcinoma was diagnosed when 100% of the malignant cells showed a squamous component (pure SCC) and MSCC was diagnosed when more than 50% of the malignant cells showed a squamous component. We analyzed the clinicopathological features, treatment methods, and outcomes of these patients.ResultsWe identified 10 (0.28%) patients with SCC or MSCC from among 3565 patients with malignant breast tumors treated at our hospital during this period. Nine patients had adenocarcinoma with squamous metaplasia, and one had pure SCC. Ultrasound showed a central cystic-necrotic component in seven tumors, and all of the tumors were negative for hormone receptors and HER2. Recurrence developed in two patients with lymph node metastasis, but not in the other eight patients. The 5-year survival rate and median survival time were 85.7% and 97 months, respectively.ConclusionsSquamous cell carcinoma or MSCC of the breast with features of the triple-negative subtype seems to be associated with a poor prognosis; however, nodenegative patients are likely to have a favorable prognosis.

Development and Validation of a Symptom Scale to Evaluate Postoperative Patients with Esophagogastric Cancer

BACKGROUND Postgastrectomy or esophagectomy symptoms can be a significant burden for patients. However, no standard scale for evaluating these symptoms has been established. We recently developed a postoperative symptom-specific scale. STUDY DESIGN After a draft scale was prepared based on a pilot study, psychometric methods were used to assess its reliability and validity. This study involved specialized and multifaceted discussions by a team consisting of gastrointestinal surgeons, gastroenterologists, psychologists, and epidemiologic researchers. The draft questionnaire included 40 questions and 3 domains. A factor analysis was carried out to refine the items and subscale design. To assess the reliability, Cronbachs alpha and score distributions were estimated. To assess the criterion-related validity, the correlations with the Short Form (SF)-12, Gastrointestinal Symptom Rating Scale (GSRS), endoscopic findings, and nutritional indicators were analyzed. RESULTS A total of 344 patients were enrolled in this study. In an exploratory factor analysis (principal factor method), the eigenvalue attenuation data showed 4 domains. The final scale, named the Esophagus and Stomach Surgery Symptom Scale (ES(4)), included 23 items and 4 domains; 7 items for cervico-thoracic symptoms, 6 for abdominal hypersensitivity symptoms, 4 for abdominal distention symptoms, and 6 items for systemic symptoms. Cronbachs alphas for these domains were 0.82, 0.81, 0.79, and 0.74, respectively. The scale scores were normally distributed, and there were significant associations with the endoscopic findings, nutritional indicators, the summary score of the SF-12, and the GSRS. CONCLUSIONS The ES(4) scale has high psychometric validity and can evaluate the profiles and severity of postoperative symptoms. This scale is applicable as an outcomes measure for various interventional studies on esophagogastric surgery aimed at alleviating postoperative symptoms.

Morbidity and mortality from a propensity score-matched, prospective cohort study of laparoscopic versus open total gastrectomy for gastric cancer: data from a nationwide web-based database

BackgroundControversy persists regarding the technical feasibility of laparoscopic total gastrectomy (LTG), and to our knowledge, no prospective study with a sample size sufficient to investigate its safety has been reported. We aimed to compare the postoperative morbidity and mortality rates in patients undergoing LTG and open total gastrectomy (OTG) for gastric cancer in prospectively enrolled cohort using nationwide web-based registry.MethodsFrom August 2014 to July 2015, consecutive patients undergoing LTG or OTG (925 and 1569 patients, respectively) at the participating institutions were enrolled prospectively into the National Clinical Database registration system. We constructed propensity score (PS) models separately in four facility yearly case-volume groups, and evaluated the postoperative morbidity and mortality in PS-matched 1024 patients undergoing LTG or OTG.ResultsThe incidence of overall morbidity were 84 (16.4%) in the OTG and 54 (10.3%) in the LTG groups (p = 0.01).The incidence of anastomotic leakage and pancreatic fistula grade B or above were not significantly different between the two groups (LTG 5.3% vs. OTG 6.1%, p = 0.59, LTG 2.7% vs. OTG 3.7%, p = 0.38, respectively). There were also no significant differences in the 30-day and in-hospital mortality rates between the two groups (LTG 0.2% vs. OTG 0.4%, p = 0.56; LTG 0.4% vs. OTG 0.4%, p = 1.00, respectively).ConclusionThe results from our nationally representative data analysis showed that LTG could be a safe procedure to treat gastric cancer compared to OTG. The indication for LTG should be considered carefully in a clinical setting.

Development and Validation of a Disease-Specific Instrument to Measure Diet-Targeted Quality of Life for Postoperative Patients with Esophagogastric Cancer

BackgroundPatients who have undergone esophagectomy or gastrectomy have certain dietary limitations because of changes to the alimentary tract. This study attempted to develop a psychometric scale, named “Esophago-Gastric surgery and Quality of Dietary life (EGQ-D),” for assessment of impact of upper gastrointestinal surgery on diet-targeted quality of life.MethodsUsing qualitative methods, the study team interviewed both patients and surgeons involved in esophagogastric cancer surgery, and we prepared an item pool and a draft scale. To evaluate the scale’s psychometric reliability and validity, a survey involving a large number of patients was conducted. Items for the final scale were selected by factor analysis and item response theory. Cronbach’s alpha was used for assessment of reliability, and correlations with the short form (SF)-12, esophagus and stomach surgery symptom scale (ES4), and nutritional indicators were analyzed to assess the criterion-related validity.ResultsThrough multifaceted discussion and the pilot study, a draft questionnaire comprising 14 items was prepared, and a total of 316 patients were enrolled. On the basis of factor analysis and item response theory, six items were excluded, and the remaining eight items demonstrated strong unidimensionality for the final scale. Cronbach’s alpha was 0.895. There were significant associations with all the subscale scores for SF-12, ES4, and nutritional indicators.ConclusionsThe EGQ-D scale has good contents and psychometric validity and can be used to evaluate disease-specific instrument to measure diet-targeted quality of life for postoperative patients with esophagogastric cancer.

Impact of postoperative complications on the colorectal cancer survival and recurrence: analyses of pooled individual patients’ data from three large phase III randomized trials

This study assessed the impact of postoperative complications on the colorectal cancer survival and recurrence after curative surgery using pooled individual patients’ data from three large phase III randomized trials. In total, 5530 patients were included in this study. The patients were classified as those with postoperative complications (C group) and those without postoperative complications (NC group). The risk factors for the overall survival (OS) and the disease‐free survival (DFS) were analyzed. Postoperative complications were found in 861 (15.6%) of the 5530 patients. The OS and DFS rates at 5 years after surgery were 68.9% and 74.8%, respectively, in the C group and 75.8% and 82.2%, respectively, in the NC group, values that were significantly different between the two groups (P < 0.001). The multivariate analysis demonstrated that postoperative complications were a significant independent risk factor for the OS and DFS. Postoperative complications can worsen the colorectal cancer survival and risk of recurrence. Surgical morbidity must be considered as a stratification factor in future phase III trials evaluating the effects of adjuvant chemotherapy on colorectal cancer.

Randomized clinical trial comparing standard diet with perioperative oral immunonutrition in total gastrectomy for gastric cancer

Total gastrectomy for gastric cancer is associated with excessive weight loss and decreased calorie intake. Nutritional support using eicosapentaenoic acid modulates immune function and limits catabolism in patients with advanced cancer, but its impact in the perioperative period is unclear.

Surgical outcomes of laparoscopic distal gastrectomy compared to open distal gastrectomy: A retrospective cohort study based on a nationwide registry database in Japan

To clarify the safety profile of laparoscopic distal gastrectomy (LDG) for gastric cancer patients, the short‐term outcome of LDG was compared to that of open distal gastrectomy (ODG) by propensity score matching using data from the Japanese National Clinical Database (NCD). We conducted a retrospective cohort study of patients undergoing distal gastrectomy between January 2012 and December 2013. Using the data for 70 346 patients registered in the NCD, incidences of mortality and morbidities were compared between LDG patients and ODG patients in the propensity score matched stage I patients (ODG: n = 14 386, LDG: n = 14 386) and stage II‐IV patients (ODG: n = 3738, LDG: n = 3738), respectively. There was no significant difference in mortality rates between LDG and ODG at all stages. Operating time was significantly longer in LDG compared to ODG, whereas blood loss and incidences of superficial surgical site infection (SSI), deep SSI, and wound dehiscence were significantly higher in ODG at all stages. Interestingly, pancreatic fistula was found significantly more often in LDG (1%) compared to ODG (0.8%) (P = .01) in stage I patients; however, it was not different in stage II‐IV patients. The length of postoperative stay was significantly longer in patients undergoing ODG compared to LDG at all stages. LDG in general practice might be a feasible therapeutic option in patients with both advanced gastric cancer and those with early gastric cancer in Japan.